The objective of our proposed research is to define the effect of Type II interferon on the cell-mediated immune response to bladder tumors and compare it with the effect of Type I interferon. To this end we will test the effect of interferon (both Type I and Type II) treatment in vitro on human mononuclear cells isolated from the peripheral blood for: (1) effect on antibody-dependent cell-mediated cytotoxicity using 253J human bladder cancer cells (2) effect on natural killer cell activity using K562 human lymphoma and 253J target cells (3) effect on the generation specific T cell mediated cytotoxicity against 253J target cells. In addition, a murine animal model system will be developed using the FANFT-induced bladder tumor, MBT-2, to evaluate the effect of interferon (Type I and Type II) in vivo and in vitro on the cell-mediated cytotoxic mechanisms listed above using appropriate mouse target cells including MBT-2 cells. Moreover, the effect of interferon-induced modulation of the immune response on the growth of transplanted MBT-2 bladder tumors in syngeneic mice will be evaluated. We will determine the dose and class (Type I or Type II) of interferon most effective for modulation of the cell-mediated responses in vitro for both the human and murine model and in vivo for the murine model. Moreover, we will determine the most effective dose and class of interferon (Type I or Type II) for prevention of the growth of transplanted MBT-2 tumors in syngeneic mice. We will determine the effect of interferon (Type I and Type II) on the inductoin of primary murine bladder tumor by FANFT.